Compliance with taking medications is a huge problem in medicine. Studies show more than half of all prescriptions are either not filled or not taken. Everyone is familiar with how easy it is to forget to take medications. This problem becomes overwhelming in complex diseases such as cancer or HIV where patients are on rigorous schedules throughout the day. Even worse is the situation where the
patient may have compromised cognitive abilities.

A new development is a chip containing networked pill that reports back on medication taking and the dissolution of the pill as reported by MIT technology review.

The company behind the technology, Proteus Biomedical, of Redwood City, CA, calls its technology the Raisin system.

In the Raisin system, each pill contains an “ingestible event marker” (IEM). The IEM consists of a sand-grain-size microchip with a thin-film battery that is activated on ingestion, as it is exposed to water. The battery, Proteus says, is nontoxic because it is made from materials similar to those in a vitamin pill. Once swallowed, the IEM sends through the body’s tissues a high-frequency electrical current that’s modulated in such a way that it provides a unique marker of the pill. It’s not an RFID technology: it uses the conductive tissues of the body to conduct the signal, rather than a radio, and the signal is confined within the body.

I previously wrote about about the development of swallowable RFID chips- a technology I like better.

Medication errors in the hospital are a major cause of preventable suffering and death. I wanted to share with you the top 6 handwriting errors of doctors in the hospital that have been banned in to prevent these errors.

First some background:  You may recall the landmark Institute of Medicine (IOM) study that found medication errors injure 1.5 million people and cost billions of dollars annually.  Their report found “the extra medical costs of treating drug-related injuries occurring in hospitals alone conservatively amount to $3.5 billion a year, and this estimate does not take into account lost wages and  productivity or additional health care costs.”  The press release of the report and summary is here and the enormous full report can be searched and read here. 

Every hospital I go to has implemented warning sheets (some in bright yellow with red stop signs on them) of the “Top 6 Forbidden Medication Orders”  These are abbreviations so often misread or mistranscribed that they have been banned in the hospital!  (not the drug or the order but the abbreviations have been banned!).  You all know how awful doctor’s handwriting is!

1. U for units with heparin insulin and pitocin can be misread as zero or cc’s causing dangerous overdoses
2. IU for nternational units can be mistaken for IV (intravenous) or 10 (ten)
3. q.d. means once a day in latin but can be mistaken for qid or qod (four times a day or every other day) if the period is written above the line
4. .1 must be written as 0.1 else 10 fold dose errors can occur
5. 1.0 should never be written – the decimal can be missed and a 10 fold dose error occur
6. morphine and magnesium can be mixed up with lethal consequences- the use of MS, MSo4, or MgSO4 have been banned

a fun view of how bad the handsriting is can be read here

There has been a flurry of debate in the military, industrial, and privacy sectors on “smartdust” and the concept of “souveillance” - but no one has yet realized this technology is poised to springboard into medicine and transform medical diagnostics.  Here I wanted to give you an overview of what this idea is and why you should keep your eye on it. 

First the general concept background:

“Smartdust” refers to micro devices (called motes) which are detection microchips each potentially the size of a speck of dust.  These grains of sand however can automatically self-network.  So far people have conceived of these low-power distributed sensing networks as having functions for climate control systems, entertainment devices and especially for big brother type surveillance systems.  

Wikipedia wrote “the smartdust concept was introduced by Kristofer S. J. Pister (University of California) in 2001 , though similar ideas existed in science fiction before then. A recent review discusses various techniques to take smartdust in sensor networks beyond millimeter dimensions to the micrometre level.  A typical application scenario is scattering a hundred of these sensors around a building or around a hospital to monitor temperature or humidity, track patient movements, or inform of disasters, such as earthquakes. In the military, they can perform as a remote sensor chip to track enemy movements, detect poisonous gas or radioactivity. The ease and low cost of such applications have raised privacy concerns.”  Beyond web 2.0 vast networks of these real time sensors are once possible technology leap of the yet inknown web 3.0.

General concept - What is Souveillance?:  is a term from Steve Mann that refers to “bottom up” surveillance using smart dust as opposed to “top down” big brother networks looking at us little people.  Here instead activities are recorded from the “perspective of a participant in the activity, typically by way of small portable or wearable recording devices that often stream continuous live video to the Internet.”  Remember the impact of the Rodney King video and of all the user generated video content on the web.  Now fast forward to a world where a large segment or even a majority of the populice had real time streaming video devices on all the time (no we are not going to discuss the porn angle on this).   This has also been called “inverse surveillance”.

Privacy advocates have been debating the merits or horrors of this type of sensor technology.   I serve on the Scientific Advisory Board of the Lifeboat Foundation which is dedicated to protecting us from future technological threats through advocacy research and education.  They have been having a heated debate on the “paradox of smart dust: we may not live without the greater security provided by smart dust, but many think they could not live with smart dust impinging on our privacy.’  

Medical Implications:  I have a vision that once this type of low power networked microsensor technology exists it will logically lead to medical sensor technology.  Potential uses I see include:

1. mass screening for infectious disease or bioterror agents.  Subjects walking into screening areas could be checked for signature molecules associated with infectious agents.  Just as we have metal detectors and now have molecular signature detectors (the litle wipe test for explosives at the airport) we will have such biological screening techology.
2. The next step will be similar screening for disease states.  Metabolomics is one such technology. Metabolomics is the study of the small-molecule metabolite byproducts left behind from cellular processes.  In simple terms it’s like examining poop.  The concept is that by measuring the collection of all the byproducts of the cells metabolism you can get a snapshot of the physiology of a cell or organism that translates to health.  One such sensor is being developed as a breath sensor for disease.  This could lead to Star Trek like medical sensors. 
3. Similarly, such technology will lead to individual genetic screening for disease risk using chips that interact with the tiny bits of DNA we shed every time we touch something. Companies commercializing this approach also already exist and have products. 
4. Taking a clue from smart dust we will then inject such sensors into our bodies where thy could circulate in the bloodstream or sit in the abdminal cavity silently sensing for disease, infectious agents, or the DNA or signature molecules of a cancer cell.  Alternative chips could exist that sit and slowly release drugs when such cell reappear once a patient is diagnosed.

I will be writing more about the details of these concepts and devices being developed in future posts now that I have introducted the concepts.  Let me know what you think! 

New Podcast Projects:  The past two weeks have been a wild ride of fun and excitement!  I have two podcast projects undergoing the final edits prior to launcing.  The first is the docinthemachine podcast focusing on the new technology and medical breakthroughts of this blog.  The second, is a major new medical education project - still under wraps.  I’ve had some major breakthroughs in the development of both.  First, we have set up a trio of partnerships.  The first is with a professional audio studio that will be the home of the podcast recording and production.  In conjunction with this we have a pro Jazz musician and his band to provide some cool smooth jazz for the show.  My hi-tech upgrade to the studio was adding a digital hybrid the telos one to the setup.  (electronics note– if looking into this check out posts on mix-minus set-ups and this great site here for audio podcasting tips).  A digital hybrid processes POTS telephone signals splitting the callers into separate audio tracks allowing high quality recording of my upcoming phone interviews.  Just as exciting is a partnership with a major medical on-line site that will handle the hosting and outreach to the medical and lay communities.  I just back back from the studio where we were recording the last bit of audio and we’ll wrap up some more interviews tomorrow before the launch.  The response so far has been overwhelming from people in the medical and tech industries and from sponsors helping out with production costs.  More news to comeas we approach launch day!

Everyone is jumping on the natural product and herbal bandwagon.  What many don’t know is that all-natural is often far from all-safe.  Almost all of these producs remain highly unregulated and untested in their claims (therefore the need for the blanket disclaimers that the products are not intended to diagnose of treat any condition). 

One of the problems with herbals is the huge rate of contamination with other ingredients.  This may be inadvertant such as mercury in fish oil capsules, heavy metals in herbs, or intentional such as the well-reported spiking of herbal viagra with real drug viagra. 

I know a manufacturer of herbal supplements.  He used to sell electronics but now sells herbal supplements.  I think it’s a more lucrative business.

Today the FDA issues a warning out arsenic contamination in mineral water.  Just realize that when these contaminations occur in herbal supplements it is often buyer beware before its discovered.  Low level contamination often is never discovered.

FDA Warns Again About Arsenic in Mineral Water  - Five Brands Recalled Within Last Month

The Food and Drug Administration (FDA) is re-issuing its warning to consumers not to drink “Jermuk” brand mineral water due to the risk of exposure to arsenic, a toxic substance and a known cause of cancer in humans. The agency is providing this information again to consumers due to an expansion of the recall initiated by the products’ importers and distributors. “Jermuk” water is imported from Armenia and distributed under different labels in California. Five brands of these products have been recalled since March 7

The good news is you probably won’t die

Although arsenic is a well known human poison, there is little chance that someone would become seriously ill after consuming the recalled products over a brief period of time (days to weeks). However, it is likely that the person would experience nausea, abdominal pain and possibly vomiting, which are indicators of arsenic toxicity.

FDA has sampled the contents of 500 milliliter (mL) green glass and/or plastic bottles of all of these brands and found they contained 454-674 micrograms of arsenic per liter of water. FDA’s standard of quality for bottled water allows no more than 10 micrograms per liter.

UPDATE:  wow two recalls in one day of natural health products!

Another fDA recall is in effect this time for some vitamins.  Unfortunately, the manufacturer faled to fully list the ingredients onthe label.  As I said it happens all the time.  This one had fish products but never listed them posing a severe allergic reaction risk for some.

FiberChoice Plus Multivitamins Issues Allergy Alert Fish Allergen Not Declared on Label

FiberChoice® fiber supplement is recalling the newest variant of FiberChoice® plus Multivitamins fiber supplement. This recall affects 90 count (16oz.) plastic bottles. 

This recall was initiated after we discovered fish gelatin, a known allergen, contained in one of the raw materials of the product, which was not declared on the product label for the multivitamins being recalled. The fish gelatin consists of the following species of fish: cod, pollock, hake, cusk, haddock, redfish, sole, and flounder.

Beppe in NYC

Now I have seen it all.  Old school med-industy came to NYC a-courtin’ new school med-bloggers last night.  I was invited to a dinner at Beppe a well ranked (not bad in Zagat - menu here) Italian restaurant near Grammercy Park by the Corporate Communication Folks at Johnson & Johnson.

The big pharma folks are exploring the blogosphere and testing the waters before they tread deeply.  Their goal was to explore the medical blogging environment and garner information to help them decide how to get involved. 

In attendance were a cadre of marketing and corporate communication execs from J&J (Heidi Youngkin (executive director/global marketing group), David Swearingen (vp corp comm), Mark Monseau (director of media relations), Jeffrey Leebaw, Ray Jordan (vp public affairs), Rob Halper (director of corporate TV) and others whose cards did not make my pocket.  They brought Adriana Lukas of mediainfluencer and bigblogcompany along with them from across the pond (UK)to try to stir-up the waters.  Nothing like having a new media marketer sitting next to an ex-official FDA marketer for fun dinner talk. 

On the medblogging side was (along with myself) Jim from BrandWeekNRX, Bob and Peter from Drugwonks and CPMI, Fard from Envisioning 2.0 and , Ed Silverman  from Pharmalot , and a highlight for me - a chance to meet my electronic pals from medgadget and blogborygmi Gene Ostrovsky and Nick Genes (of Grand Rounds Fame). 

L to R Gene Me and Nick!-

guess who works in the ER, who is a computer programmer, and who came from a full day of patient office hours?

The conversations focused on how industry could partner with bloggers, should they give emplyees free-reign to blog about their work (sure the attorney with NDA in hand will love that), and how the public is using inernet and blog med info.  Personally, I spoke about what I see in patient disease chats and discussion forums.  There is so much great information but so much disinformation and inaccuracies.  I volunteer my time to answer medical questions on forums like these such as ATIME.  I believe industry can play a role to foster moderation of information (think Citizendium to Wikipedia).  A bit of industry support could help get a panel of docs pharmacists nurses etc time to respond to the mass of information requests and provide an objective commentary (when requested).  Real partnerships between industry and patient groups could be fostered on education and not just financing. 

I also enjoyed picking Peter Pitts (former FDA’s “chief messaging officer,” serving under Commissioner Mark B. McClellan) brain about 1) why the FDA and legislature is not tackling the herbal and alternative medicine horrors MD’s are seeing (ie who’s getting the payoff) and 2) if FDA does not think herbals are drugs to be regulated why they think sperm, eggs, and embryos are (but that the subject of a whole series of posts to come…)

UPDATE- wow some people are actually blogging about the dinner and who did or did not get invited.  You can see the Post on Rost’s whistleblower site and my comments back here

this stuff makes crank look like candy

Gizmag reports on the further evolution of no-sleep performance enhancing drugs.

The original version of these substances was the “time-shifting” drug, Modafinil that enables you to stay awake for 40+ hours with close to full mental capacity and with few side effects. (produced by Cephalon as PROVIGIL®, MODIODAL® in France and VIGIL® in Germany, for excessive sleepiness associated with narcolepsy and for “shift work sleep disorder” - hear that you medical interns?- web site advertises free 7 day trial supply).  

This is precisely the substance the the former chief medical director of the olympic committee spoke to me of.  He asked - once this stuff hits the street don’t you think a majority of college students would use it to perform better on exams?   The military sure thinks its a god idea for soldiers and pilots.  You can read my thoughts on how far people will go in the future to enhance their bodies here.  If you think plastic surgery is the rage of body enhancement - wait until we get performance enhancing bionics and cognitive enhancing drugs and implants!

The drug is a eugeroic and offers improved memory, mood enhancement, improved alertness and cognitive powers without any of the nasty side effects and mass murder of speed and crank.

What’s a Eugeroic you ask?  - Literally the term means “Good Arousal” .  They are a class of novel stimulants that produce long-lasting mental arousal. They are unique in producing hypervigilence and alertness without peripheral effects or addidition of usual stimulants.  Strangely, they have minimal effect on sleep structure, and do not cause rebound hypersomnolence (crashing).

You might also be interested in Ampakines are similar but also cause memory enhancement (just a bit of abuse potential there).  One of these - a drug code-named CX717 from Cortex - reportedly enabled sleep deprived rhesus monkeys to outperform rested normal monkeys on memory tasks. 

Under carefully controlled conditions and constant medical monitoring, the monkeys were individually sleep-deprived for 30-36 hours and re-tested at that time. When monkeys are sleep deprived their performance accuracy is reduced by 15-25%, and their reaction times slow by at least 50%. A dose of 0.8 mg/kg of CX717 completely reversed the performance deficits associated with sleep-deprivation. In addition, specific brain EEG changes that occur after sleep deprivation were returned to the non-sleep-deprived state in the CX717 group, but not in the control group. Thus, CX717 counteracted the effects of periods of prolonged sleep deprivation when given immediately before testing  

Not surprisingly, DARPA had a hand in these experiments.

Man, I remember as an intern a 43 hour shift I once did (Friday AM straight to Monday afternoon).  By Sunday I was practically hallucinating, everthing was in slow motion , and there was a constant sound of running water…  I predict these drugs have an abuse potential greater than any drug since alcohol.

I hear there is a new super eugeroic called armodafinil coming down the pike with even more potent effects.

FDA reform continues in new programs to track drug safety and share data with the public.

The FDA has a three part mission but has been criticized in focusing on only one of these.  The missions of the FDA are:

1) To promote and protect the public health by helping safe and effective products reach the market in a timely way (however this is the focus of what they do now- new drug approval). 
2) To monitor products for continued safety after they are in use (new programs are to focus on this)
3) To help the public get the accurate, science-based information needed to improve health (new programs are to focus on this)

Why is post-approval FDA drug safety monitoring important for the US population? A September 2006 Institute of Medicine report recommended 25 changes to ensure the safety of prescription drugs. FDA has responded with an announcement that it will establish a pilot program that will publish a “report card” that reviews the side effects, use and latest research on two or three new drugs 18 months after they reach the market.  The IOM report’s major recommendations are:

• A requirement that packages for new prescription drugs for two years include a symbol to inform patients that the safety profile of the medication is not fully established
• A restriction on direct-to-consumer advertisements for new prescription drugs for the first two years
• A requirement that FDA reevaluate the safety and effectiveness of new prescription drugs within five years of approval
• Additional authority for FDA to impose fines on pharmaceutical companies
• A requirement that pharmaceutical companies register all clinical trials they sponsor in a federal database accessible by patients and health care professionals
• A requirement that most FDA advisory committees members have no potential conflicts of interest with the pharmaceutical industry
• A six-year term of office for the FDA commissioner.

kaisernetwork.org further comments on the FDA deficiencies leading to the recommendations:

Committee Chair Sheila Burke, said “We found an imbalance in the regulatory attention and resources available before and after approval. Staff and resources devoted to pre-approval functions are substantially greater. Regulatory authority that is well-defined and robust before approval diminishes after a drug is introduced to the market” (Bridges, AP/Chicago Sun-Times, 9/24).

Post marketing approval is vital since the clinical trials that lead to drug approval are so tightly constructed that they often have limited applicability to the general real-world population.  As a clinician and investigator I see this every day.  This was one of the reasons why in years past so few drug trials included women and minorities - whose different genetics and metabolism led to unexpected results and side-effects when they took the drugs as patients. 

Committee member R. Alta Charo, a bioethicist at the University of Wisconsin-Madison, said that clinical trials conducted prior to the approval of new prescription drugs might not provide an accurate safety profile for the general population. “A drug tested in a few hundred or thousand people is very different when used by millions, especially over long periods of time and in conjunction with other supplements,” Charo said. Charo also said that FDA has “a lack of collaboration among divisions, tensions (and) inappropriate management” (Washington Post, 9/23).

FDA picks three areas to focus upon out of the 25 IOM recommendations.

1. Strengthening the science used during product reviews and finding new tools to detect safety issues from preclinical testing through postmarketing.

2. Improving communications, especially about risk, to patients, physicians, and other interested parties.

3. Improving management practices.

Funding to come from new fees on drug makers Under the Prescription Drug User Fee Act the FDA aims to collect $29 million from drug makers over 5 years specifically for postmarketing safety programs.

New Drug Report Card reports ognews

Key among the new initiatives announced in late January is a “report card” on the postmarketing safety of new molecular entities. FDA has proposed a pilot feasibility study this year. These periodic, regularly scheduled reports would encompass data from the Adverse Events Reporting System (AERS), epidemiologic studies, postmarketing clinical trials, and from “mining” of various other databases. The first report would come 18 months after a drug’s launch. The goal of this effort is “to identify potential safety concerns early in the product life cycle,” according to the FDA.

Hearings to look into public safety reporting system

The FDA also said it would hold a public meeting in early March to explore the creation of a nationwide public-private medical product safety network. The agency envisions a network that would let both health care providers and regulators rapidly collect and exchange information about adverse events—and would do so at the point of care to help providers make better-informed treatment decisions

Senators want to go even further

Sen. Christopher J. Dodd (D-Conn.) Sen. Chuck Grassley (R-Iowa) are introducing a bill that would “revamp and prioritize the postmarket surveillance process within the Food and Drug Administration.”  The Food and Drug Administration Safety Act, would establish a Center for Postmarket Evaluation and Research for Drugs and Biologics. The Center would report directly to the FDA commissioner.

Further FDA Initiatives for this new surveillance reported by medical news today

• Collaborate with the Department of Veterans Affairs, CMS and private insurers to collect data on any problems that physicians and patients encounter with medications
• Increase transparency in the process of how the agency selects advisory panel members (Vedantam, Washington Post, 1/31)
• Create a new advisory panel that will recommend ways for the agency to improve how it communicates with the public about potential drug risks (New York Times, 1/31)
• Publish periodic newsletters on its Web site to update the public on post-market reviews of medications
• Implement organizational changes to improve communication between agency employees who monitor drug approvals and those who monitor post-market safety (Rubin, USA Today, 1/31)
• Modernize the “adverse events” database so that potential problems are easier to recognize (Alonso-Zaldivar, Los Angeles Times, 1/31)
• Renew the agency’s focus on scientific endeavors, including the creation of a database of genetic codes associated with poor drug outcomes and developing screening tests to identify patients at highest risk for adverse events (New York Times, 1/31)
• Appoint a chief medical officer to oversee scientific operations (Pugh, Miami Herald, 1/31)

They also report FDA claims inadequate funds or authority to enact all IOM recommendations

FDA’s proposals did not address a number of the IOM report’s recommendations, some of which would require congressional action, the Times reports (New York Times, 1/31). For example, FDA did not say it would restrict direct-to-consumer advertising of new prescription drugs or require label changes that would alert consumers if treatments had been on the market for less than two years (Miami Herald, 1/31). FDA Commissioner Andrew von Eschenbach said the agency considers the IOM report “a substantial amount of advice” but not a “rigid blueprint” (USA Today, 1/31). In its response to the IOM report, FDA said it “believes it has the statutory and regulatory authority needed to carry out its commitment to ensure drug safety,” although it added that it needs more funding to do so (Wall Street Journal, 1/31).

Last Minute Update Today From Washington Post: Experts recommend that FDA not allow drug companies to keep drug research study results secret. 

I have seen this happen too many times!  I can recall being involved or hearing about studies of both drugs and devices for FDA approval that did not go as expected and did not show the results the manufacturer expected.  Unfortunately, all too often the compnay contract with the physician researcher or university stipulates that the doc is not free to publish the data on his own.  In effect a virtual gag order on the negative results.  I quickly learned at Yale that for intellectual and academic integrity the University would insist we not have these clauses.  Washington Post reports:

Changes need to be made to the U.S. Food and Drug Administration’s policy regarding the confidentiality of drug safety data from clinical trials, say researchers at the Harvard School of Public Health and Brigham and Women’s Hospital in Boston. 

Current rules allow drug companies to keep data secret, which prevents the public from learning about dangerous side effects of drugs, the researchers said. Allowing greater public access to this data would enable outside experts to independently evaluate the data and perhaps detect risks sooner.

They report that FDA supports blocking access to the information

The FDA and the drug companies say drug information needs to be protected so that competing manufacturers can’t use the data to produce competing versions of drugs. However, the commentary authors argue that making drug safety data public rarely poses a risk to a company’s confidential research and development programs.

“The legal question is whether the information will give other drug companies an unfair competitive advantage. But it is strange to argue that evidence that a drug is harmful will enable others to develop similar drugs,” noted co-author Michelle Mello, an associate professor of health policy and law at the Harvard School of Public Health.

and the authors recommend:

A heavier burden of proof be placed on companies to show competitive harm if safety data are released.The FDA replace the current Summary Basis of Approval with a more comprehensive public document that includes all safety data.Congress passes a law that requires public disclosure of safety data if the FDA fails to take action.

“Safety data from drug clinical trials have important ramifications for public health. The government should do as much as it can to ensure full disclosure of the information,” Kesselheim said